Primary T-cell Vitreoretinal Non-Hodgkin Lymphoma: A Case Report and Literature Review.

A 72-year-old Chinese male presented with unilateral left eye panuveitis, then diagnosed as bilateral T-cell primary vitreoretinal lymphoma (T-PVRL) through chorioretinal biopsy and immunohistochemistry. No CNS nor systemic involvement was found at diagnosis. Despite initiating intravenous and intrathecal chemotherapy and intravitreal methotrexate, the disease eventually spread to the fellow eye with subsequent recurrence and systemic metastasis. To our knowledge, no cases of T-PVRL treated in a silicone-filled eye were reported in the literature. T- PVRL is exceedingly rare, with most PVRL being the malignant B-cell variant. This case highlights the challenges encountered throughout the treatment course of this aggressive entity, including the administration of intravitreal methotrexate in a silicone oil-filled eye. The poor overall survival rate and grim prognosis of T-PVRL are highlighted. Therefore, we recommend prompt tissue biopsy and immediate initiation of systemic chemotherapy and intravitreal methotrexate.

Premature Ocular Aging Features in Childhood Acute Lymphoblastic Leukemia Survivors.

Purpose: Childhood cancer survivors (CCS) demonstrate features of premature aging in a multitude of organ systems. The aim of this pilot study is to determine the presence of premature ocular aging features in CCS, specifically childhood acute lymphoblastic leukemia (ALL) survivors. Methods: This prospective case-control study was conducted over a period of 21 months, starting July 2015 till March 2017. A total of 59 childhood ALL survivors who attended the Paediatric Oncology Clinic of University Malaya Medical Centre (UMMC) and 48 age, race, and gender-matched controls went through a series of ocular examinations and tests. Inclusion criteria used to recruit survivors were age above 16 years, history of ALL in childhood, completion of treatment for ALL, and a remission period of at least 5 years. Patients with ocular disease and those who received hematopoietic stem cell transplantation were excluded. The parameters measured were visual acuity, amplitude of accommodation, pupil cycle time (PCT), and tear break-up time (TBUT). Results: Survivors of childhood ALL demonstrated significant differences in amplitude of accommodation, PCT, and TBUT compared to age-matched controls. Survivors had a lower median (interquartile range [IQR]) amplitude of accommodation compared to controls (11.0 D [9.0-13.0] vs. 12.0 D [10.5-15]; p = 0.045). Survivors also showed a longer median (IQR) PCT in comparison to controls (931.00 mseconds (857.00-1063.00) vs. 875.50 mseconds (825.75-966.00); p = 0.024). In addition, median (IQR) TBUT was worse in survivors in comparison to the control group (9 seconds [6-13] vs. 11 seconds [10-15]; p = 0.001). Conclusion: Survivors of childhood ALL demonstrate premature ocular aging features compared to age-matched controls. Thus, survivors may benefit from having ocular examinations as part of their routine late-effects screening to detect age-related ocular morbidities early in its course.

Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress.

AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic ß-cells. By culturing rat pancreatic ß-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic ß-cells. We postulate that miR-15a, produced in pancreatic ß-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic ß-cell-specific miR-15a-/- mice. INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications. CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.